Mitochondrial thioredoxin reductase 2 is elevated in long‐lived primate as well as rodent species and extends fly mean lifespan |
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Authors: | Andrew M. Pickering Marcus Lehr Christi M. Gendron Scott D. Pletcher Richard A. Miller |
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Affiliation: | 1. Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA;2. Department of Pathology, University of Michigan, Ann Arbor, MI, USA;3. Geriatrics Center, University of Michigan, Ann Arbor, MI, USA;4. Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA |
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Abstract: | In a survey of enzymes related to protein oxidation and cellular redox state, we found activity of the redox enzyme thioredoxin reductase (TXNRD) to be elevated in cells from long‐lived species of rodents, primates, and birds. Elevated TXNRD activity in long‐lived species reflected increases in the mitochondrial form, TXNRD2, rather than the cytosolic forms TXNRD1 and TXNRD3. Analysis of published RNA‐Seq data showed elevated TXNRD2 mRNA in multiple organs of longer‐lived primates, suggesting that the phenomenon is not limited to skin‐derived fibroblasts. Elevation of TXNRD2 activity and protein levels was also noted in liver of three different long‐lived mutant mice, and in normal male mice treated with a drug that extends lifespan in males. Overexpression of mitochondrial TXNRD2 in Drosophila melanogaster extended median (but not maximum) lifespan in female flies with a small lifespan extension in males; in contrast, overexpression of the cytosolic form, TXNRD1, did not produce a lifespan extension. |
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Keywords: | aging
Drosophila
lifespan mice mitochondria oxidative stress primates rodents thioredoxin TXNRD2 Trxr2 TXN |
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